USP 467 Flexibility

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Greg Pronger
Greg Pronger's picture
USP 467 Flexibility

In considering some of the issues regarding this method, a potential solution would seem to be the use of vacuum distillation rather than headspace. The USEPA developed this technique to allow analysis of oily and other high matrix samples for volatile compounds including compounds with high water solubility and (or) polarity.
What I do not have experience with the the level of flexibility and what are the procedures for use of alternative technologies.
Info on vacuum distillation could be found at: (USEPA Method) (Vendor)

Dr. Analytical
Dr. Analytical's picture

I would like to say that FDA is more tolerant of change than EPA, but in practice the differences are not so great.  However, the USP methods are an interesting area.  If you folllow the method "as written" (which is difficult in some cases), and have verified your ability to produce acceptable results, then the results are generally not questioned.
The method language seems to allow some variation in operating parameters to suit individual instruments.  But just how far you can go before you have a new method is subject to some debate.  If you go too far, then you really have to "validate" the method, rather than verify (meaning more work).
To explore other technologies entirely should be acceptable, however full validation would be required.  Can your technique handle the low levels needed for the Class 1 solvents (< 1 ppm for benzene)?  If so, you could generate some data and pass it by either USP or the regulatory agency (Latter approach will probably be faster).  Having some data makes a huge difference.
Does this help?

Greg Pronger
Greg Pronger's picture
The technique is similar to

The technique is similar to either dynamic headspace or tradtional purge and trap, in that it attempts an exhaustive transfer of the target analyte onto a trap (for vacuum distillation this is a cold trap allowing more reactive species to be measured). Because of this, PPB levels are typical (generally analogous levels of detection to P&T) except that it works better than p&t for poor purgers (water soluble) and reactive compounds.
For the types of matrices that are encountered for USP applications, a technique that does a good job of mitigating matrix effects while achieving PPB levels of sensitivity would seem beneficial.
From what you indicate, it would seem a full validation would be necessary. It would seem though that an improved level of detection may be beneficial.

8261 Analyte & CAS No
8261 Analyte & CAS No

Acetone 67-64-1
1,4-Dioxane 123-91-1

Acetonitrile 75-05-8
Ethanol 64-17-5

Acetophenone 98-86-2
Ethyl acetate 141-78-6

Acrolein 107-02-8
Ethylbenzene 100-41-4

Acrylonitrile 107-13-1
Ethyl t-butyl ether (ETBE) 637-92-3

Allyl chloride 107-05-1
Ethyl methacrylate 97-63-2

t-Amyl ethyl ether (TAEE) 919-94-8
Hexachlorobutadiene 87-68-3

t-Amyl methyl ether (TAME) 994-05-8
2-Hexanone 591-78-6

Aniline 62-53-3
Iodomethane 74-88-4

Benzene 71-43-2
Isobutyl alcohol 78-83-1

Bromochloromethane 74-97-5
Isopropylbenzene 98-82-8

Bromodichloromethane 75-27-4
p-Isopropyltoluene 99-87-6

Bromoform 75-25-2
Methacrylonitrile 126-98-7

Bromomethane 74-83-9
Methyl t-butyl ether (MTBE) 1634-04-4

2-Butanone 78-93-3
Methylene chloride 75-09-2

t-Butyl alcohol (TBA) 75-65-0
Methyl methacrylate 80-62-6

n-Butylbenzene 104-51-8
1-Methylnaphthalene 90-12-0

sec-Butylbenzene 135-98-8
2-Methylnaphthalene 91-57-6

tert-Butylbenzene 98-06-6
4-Methyl-2-pentanone (MIBK) 108-10-1

Carbon disulfide 75-15-0
Naphthalene 91-20-3

Carbon tetrachloride 56-23-5
N-Nitrosodibutylamine 924-16-3

Chlorobenzene 108-90-7
N-Nitrosodiethylamine 55-18-5

Chlorodibromomethane 124-48-1
N-Nitrosodimethylamine 62-75-9

Chloroethane 75-00-3
N-Nitrosodi-n-propylamine 621-64-7

Chloroform 67-66-3
N-Nitrosomethylethylamine 10595-95-6

Chloromethane 74-87-3
Pentachloroethane 76-01-7

2-Chlorotoluene 95-49-8
2-Picoline 109-06-8

4-Chlorotoluene 106-43-4
Propionitrile 107-12-0

1,2-Dibromo-3-chloropropane 96-12-8
n-Propylbenzene 103-65-1

Dibromomethane 74-95-3
Pyridine 110-86-1

1,2-Dichlorobenzene 95-50-1
Styrene 100-42-5

1,3-Dichlorobenzene 541-73-1
1,1,2,2-Tetrachloroethane 79-34-5

1,4-Dichlorobenzene 106-46-7
Tetrachloroethene 127-18-4

cis-1,4-Dichloro-2-butene 764-41-0
Tetrahydrofuran 109-99-9

trans-1,4-Dichloro-2-butene 110-57-6
Toluene 108-88-3

Dichlorodifluoromethane 75-71-8
o-Toluidine 95-53-4

1,1-Dichloroethane 75-34-3
1,2,3-Trichlorobenzene 87-61-6

1,2-Dichloroethane 107-06-2
1,2,4-Trichlorobenzene 120-82-1

1,1-Dichloroethene 75-35-4
1,1,1-Trichloroethane 71-55-6

trans-1,2-Dichloroethene 156-60-5
1,1,2-Trichloroethane 79-00-5

cis-1,2-Dichloroethene 156-59-2
Trichloroethene 79-01-6

1,2-Dichloropropane 78-87-5
Trichlorofluoromethane 75-69-4

1,3-Dichloropropane 142-28-9
1,2,3-Trichloropropane 96-18-4

2,2-Dichloropropane 594-20-7
1,2,4-Trimethylbenzene 95-63-6

1,1-Dichloropropene 563-58-6
1,3,5-Trimethylbenzene 108-67-8

cis-1,3-Dichloropropene 10061-01-5
Vinyl chloride 75-01-4

trans-1,3-Dichloropropene 10061-02-6
o-Xylene 95-47-6

Diethyl ether 60-29-7
m-Xylene 108-38-3

Diisopropyl ether (DIPE) 108-20-3
p-Xylene 106-42-3